The functional consequences of the interactions between insulin-like growth factors (IGFs), insulin-like growth factor binding proteins (IGFBPs) and vitronectin (VN) and their involvement in skin

摘要: The insulin-like growth factor (IGF) system plays an important role in a number of disease states, such as cancer, and has also been implicated wound burn healing processes. Two IGF receptors, the type-1 type-2 well six binding proteins (IGFBP-1 to 6), have established roles mediating activity. Earlier studies this laboratory demonstrated that IGF-II binds extracellular matrix (ECM) protein vitronectin (VN), although IGF-I does not bind directly VN it can indirectly via specific IGFBPs. Therefore aim research described thesis was determine whether binary ternary complexes IGF-I/II, IGFBPs affect human keratinocyte cell function. strategy pre-binding these culture dishes adopted study attempt more accurately reflect environment vivo. These complex comprised IGF-I, IGFBP-2, or 3, 4, 5 significantly stimulated HaCaT de novo synthesis line. Interestingly, latter experiments large increases were observed using complexes, IGF-I/IGFBP alone responsible for significant responses are mediated MAPK signaling pathway. In addition, both dimeric trimeric enhanced migration through 12 μm TranswellsTM. Unlike assays, critically migratory highlighting integrins play migration. Cell attachment assays on other hand interactions IGFs with did attachment. data encompassed within represent first provide functional interaction between IGFs, keratinocytes. Taken together results suggest IGF/IGFBP/VN may hold great potential situations where proliferation is required, skin engineering applications.